Immunology
1. Self-Nonself Model of Immunity (1940s–1990s) → Replaced by Danger Model
- What it was: The idea that the immune system simply distinguishes between “self” (body’s own cells) and “nonself” (foreign invaders like bacteria or viruses).
- Why it collapsed: Polly Matzinger’s Danger Model (1994) proposed that the immune system responds not just to “nonself” but to danger signals, such as cellular stress, necrosis, and inflammation. This better explains autoimmune diseases and immune tolerance.
2. Hygiene Hypothesis (1980s) → Refined with Microbiome Research
- What it was: The hypothesis suggested that lack of childhood exposure to germs increased susceptibility to allergies and autoimmune diseases.
- Why it collapsed: While partially true, modern research on the gut microbiome (2010s) refined this view, showing that a balanced microbiome (rather than just germ exposure) is critical for immune development.
3. Original Antigenic Sin Theory (1950s) → Modified by Immunological Plasticity
- What it was: The idea that once the immune system encounters a pathogen, it preferentially responds to the first strain encountered, even if a new variant emerges.
- Why it collapsed: Studies on flu, COVID-19, and other viruses show that the immune system is more adaptive and plastic than originally thought, though antigenic imprinting still plays a role.
4. Th1/Th2 Dichotomy (1980s–2000s) → Expanded to Include Th17, Tregs, and More
- What it was: Initially, helper T cells (CD4+) were classified into Th1 (cell-mediated immunity) and Th2 (antibody-mediated immunity).
- Why it collapsed: The discovery of Th17 cells (involved in autoimmune diseases) and T regulatory cells (Tregs, crucial for immune suppression and tolerance) in the 2000s showed that the immune system is far more complex than a simple Th1/Th2 balance.
5. Complete Eradication of Infectious Diseases by Vaccination (Overly Optimistic View in the 1960s–1980s)
- What it was: After the success of smallpox eradication (1980), scientists thought other infectious diseases (like measles and polio) would be fully eradicated soon.
- Why it collapsed: Factors like vaccine hesitancy, viral evolution, and zoonotic spillover events (e.g., COVID-19, influenza mutations) have shown that infectious diseases persist despite vaccination efforts.
6. Humoral vs. Cellular Immunity as a Strict Dichotomy (Mid-20th Century) → Recognized as Interdependent
- What it was: Early immunologists thought of antibody-driven (humoral) immunity and T-cell-driven (cellular) immunity as two separate branches.
- Why it collapsed: Modern immunology has shown strong crosstalk between B cells, T cells, and innate immune responses. For example, T follicular helper cells (Tfh) are critical for antibody production, blurring the line between cellular and humoral immunity.
Biochemistry and immunology have seen massive shifts in understanding since 1945, often due to new experimental techniques (e.g., PCR, genome sequencing, CRISPR) and conceptual breakthroughs. Many ideas that were once foundational have been refined, replaced, or completely abandoned as science progresses.